Toxicology 301 (2012) 21–32 Contents lists available at SciVerse ScienceDirect Toxicology jou rn al hom epage: www.elsevier.com/locate/toxicol Human skin penetration of selected model mycotoxins Jente Boonen a , Svetlana V. Malysheva b , Lien Taevernier a , José Diana Di Mavungu b , Sarah De Saeger b , Bart De Spiegeleer a,∗ a Drug Quality and Registration (DruQuaR) Group, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium b Laboratory of Food Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium a r t i c l e i n f o Article history: Received 3 April 2012 Received in revised form 24 May 2012 Accepted 19 June 2012 Available online 27 June 2012 Keywords: Mycotoxins Dermal exposure Risk assessment Transdermal penetration Human skin a b s t r a c t Dermal exposure data for mycotoxins are very scarce and fragmentary, despite their widespread skin contact and hazard toxicity. In this study, the transdermal kinetics of aflatoxin B1 (AFB1), ochratoxin A (OTA), fumonisin B1 (FB1), citrinin (CIT), zearalenone (ZEA) and T-2 toxin (T-2) were quantitatively evaluated, using human skin in an in vitro Franz diffusion cell set-up. All mycotoxins penetrated through the skin, except for FB1, which showed concentrations in the receptor fluid below the LoD, resulting in a K p < 3.24 × 10 -6 cm/h. OTA showed the highest permeation (K p = 8.20 × 10 -4 cm/h), followed by CIT (K p = 4.67 × 10 -4 cm/h). AFB1 and ZEA showed lower permeability rates (K p = 2.11 and 2.33 × 10 -4 cm/h, respectively). T-2 was found to have the lowest permeability (K p = 6.07 × 10 -5 cm/h). From literature- based mycotoxin-concentrations, dermal contact surface, exposure time and apparent K p ’s obtained in this study, the daily dermal exposure (DDE) in two industrial and one residential scenario was estimated. Dermal exposure to the DNA-reactive genotoxic carcinogenic AFB1 can lead to a health risk for agricultural workers which are exposed to a mycotoxin contaminated solution in a worst case situation. For all the other investigated mycotoxins, no significant health risk is calculated after dermal contact in neither agricultural nor residential environments. © 2012 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Mycotoxins are secondary metabolites produced by fungi (Braese et al., 2009). The worldwide contamination of these ubiq- uitous natural products in food, feed and environment, including indoor surfaces and particles, form a health risk for animals as well as humans (Zain, 2011). Over 400 mycotoxins are identified, but there are indications that thousands of mycotoxins exist (Nielsen and Smedsgaard, 2003). Very often, more than one mycotoxin is found on the contaminated substrate. The question arises to what extent these mycotoxins form a health risk (Creppy, 2002; Hussein and Brasel, 2001; Muro-Cacho et al., 2004; Peraica et al., 1999). Absorption of mycotoxins often occurs by ingestion of contam- inated food, but can also be via inhalation or dermal exposure to air and dust containing mycotoxins. However, there are many Abbreviations: AFB1, aflatoxin B1; AFB2, aflatoxin B2; CIT, citrinin; FB1, fumon- isin B1; FB2, fumonisin B2; FDC, Franz diffusion cell; OTA, ochratoxin A; OTB, ochratoxin B; T-2, T-2 toxin; ZEA, zearalenone; SA, skin area; ED, exposure dura- tion; EF, exposure frequency; EV, event frequency; tevent , event duration; BW, body weight; AT, averaging time; TDI, tolerable daily intake; NCRI, negligible cancer risk intake; NOAEL, no observed adverse effect level; LOAEL, lowest observed adverse effect level; BMD, benchmark dose. ∗ Corresponding author. Tel.: +32 9 264 81 00; fax: +32 9 264 81 93. E-mail address: bart.despiegeleer@ugent.be (B. De Spiegeleer). uncertainties about the toxin fraction absorbed and hence, about the true impact of mycotoxin exposure via the different routes. Mayer et al. (2007) identified the research need of exposure assess- ment to mycotoxins. The health risk of mycotoxins was generally assessed via the oral route. Recently, the inhalation route is also gaining scientific interest (Halstensen, 2008; Hardin et al., 2009; Soroka et al., 2008; Tangni and Pussemier, 2007; Terr, 2009). The skin however, is almost unexplored as exposure route. Although the skin forms a natural barrier for exogenous compounds, the low molecular weight mycotoxins are lipid soluble, possessing appropriate properties for occupational as well as accidental skin penetration. Compared to the amount of identified mycotoxins and their health risk, to date, skin permeability data of mycotox- ins is nevertheless quite limited but highly wanted (Degen, 2011). Supplementary Table S1 gives a literature overview of the skin related mycotoxin research. Anno end 2011, about 50, mostly frag- mentary studies, have evaluated the (trans)dermal behaviour and resulted effects of less than 20 mycotoxins, mainly AFB1 and T-2 toxin. The majority of these studies, about 70%, describe in vivo ani- mal methods, frequently using rats, mice, pigs and rabbits. Half of the remaining studies have also applied in vitro animal skin models and very often, quantitative kinetics are lacking. Therefore, in this study, the transdermal kinetics of mycotoxins were quantitatively evaluated using excised human skin in an in vitro Franz diffusion cell (FDC) set-up. 0300-483X/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tox.2012.06.012